Dose variations in tumor volumes and organs at risk during IMRT for head-and-neck cancer

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1 JOURNAL OF APPLIED CLINICAL MEDICAL PHYSICS, VOLUME 13, NUMBER 6, 2012 Dose variations in tumor volumes and organs at risk during IMRT for head-and-neck cancer Mercè Beltran, 1a Mónica Ramos, 2 Juan José Rovira, 1 Santiago Perez-Hoyos, 3 Marc Sancho, 1 Enrique Puertas, 2 Sergi Benavente, 2 Mercè Ginjaume, 4 Jordi Giralt 2 Servei de Física, 1 Servei d Oncologia Radioteràpica, 2 Servei de Medicina Preventiva i Salut Pública, 3 Hospital Universitari Vall d Hebron, Universitat Autònoma de Barcelona, Barcelona 08035, Spain; Institut de Tècniques Energètiques, 4 Universitat Politècnica de Catalunya, Campus Diagonal Sud Edifici PC, Barcelona 08028, Spain mbeltran@vhebronnet Received 28 July, 2011; accepted 21 July, 2012 Many head-and-neck cancer (HNC) patients treated with radiotherapy suffer significant anatomical changes due to tumor shrinkage or weight loss The purpose of this study was to assess dose changes over target volumes and organs at risk during intensity-modulated radiotherapy for HNC patients Sixteen HNC IMRT patients, all requiring bilateral neck irradiation, were enrolled in the study A CT plan was performed and the initial dose distribution was calculated During the treatment, two subsequent CTs at the 15th ( ) and 25th ( ) fractions were acquired The initial plan was calculated on the, and dose-volume differences related to the CT plan were assessed For target volumes, mean values of nearmaximun absorbed dose (D 2% ) increased at the 25th fraction, and doses covering 95% and 98% of volume decreased significantly at the 15th fraction Contralateral and ipsilateral parotid gland mean doses increased by 61% (range: -54, 235%) and 47% (range: -91, 223%), respectively, at The D 2% in the spinal cord increased by 18 Gy at Mean absorbed dose increases at were observed in: the lips, 38% and 53%; the oral cavity, 35% and 25%; and lower middle neck structure, 19% and 16% Anatomical changes during treatment of HNC patients affect dose distribution and induce a loss of dose coverage to target volumes and an overdosage to critical structures Appropriate organs at risk have to be contoured and monitored in order to know if the initial plan remains suitable during the course of the treatment Reported dosimetric data can help to identify patients who could benefit from adaptive radiotherapy PACS numbers: 8753Kn, 8755Dk Key words: head-and-neck cancer, IMRT, dose-volume changes, organs at risk I Introduction The benefit of intensity-modulated radiation therapy (IMRT) in the treatment of head-and-neck cancer (HNC) has been demonstrated in numerous studies (1-3) Highly conformal radiation allows for a high dose to high-risk areas, whilst sparing adjacent organs at risk (OAR) such as the parotid glands Clinical studies have shown that IMRT reduces grade-3 xerostomia in comparison to three-dimensional conformal radiotherapy (3D CRT) (4,5) For that reason, IMRT has become the standard treatment in many centers IMRT dose distributions, with steep dose gradients, are very sensitive to geometrical uncertainties, and hence, deviations between planned and delivered dose distributions have to be minimized One way of improving the treatment a Corresponding author: Mercè Beltran, Servei de Física, Hospital Universitari Vall d Hebron, Universitat Autònoma de Barcelona, Passeig Vall d Hebron , Barcelona 08035, Spain; phone: ; fax: ; mbeltran@vhebronnet

2 102 Beltran et al: Dose variations in H&N IMRT 102 accuracy is to reduce geometrical errors Rigid errors, such as setup, have been extensively studied Mechalakos et al (6) for instance evaluated the interfraction and intrafraction errors in treatments of HNC and compared their results with previous studies from others authors Margins are added to clinical volumes in order to take into account geometrical uncertainties These planning margins are commonly calculated from measured systematic and random geometrical errors (7) However, it is well known that many HNC patients treated with radiotherapy (RT) suffer significant anatomical changes due to tumor shrinkage or weight loss Several scheduled rescanning studies have evaluated these volumetric changes in both target volumes and normal tissues, (8-11) mostly on the parotid glands and their consequent effects on dose distribution (12-15) The information obtained from these studies indicates that anatomical changes during the treatment can cause deviations between the planned and delivered dose, specifically reducing dosage to target volumes whilst increasing dosage to critical structures Adaptive RT based on replanning during treatment is a common strategy to minimize the effect of anatomical changes over dose distribution, (16,17) although identifying which patients in particular could best benefit from replanning is, as yet, undetermined Ahn et al (18) indicated the need for an accurate determination of anatomical changes and their consequent dosimetric parameters as a prime factor in the determination of any subsequent replanning The purpose of the present study was to analyze volume variation repercussions on the dose distribution in both PTVs and organs at risk The use of IMRT implies the irradiation of more OARs than conventional 3D CRT Therefore, beside typical susceptible organs such as the eyes, spinal cord, parotid glands, and mandible, we have also included additional OARs such as the oral cavity, cochleae, lips, brain, brainstem, and lower middle neck structures The influence of anatomical changes over dose distribution on these structures has not, until now, been reported in previous studies The study was experimental and patients were treated without replanning II Materials and Methods A Eligibility criteria Patients were required to have a histologically proven diagnosis of HN squamous cell carcinoma of the head and neck, staged T3-T4 N0 or T1-T4 N1-N3 Patients were aged 18 years or over, with a Karnofsky performance score of 80% Eligibility criteria also included bilateral neck irradiation The protocol was approved by the local Ethics Committee All enrolled patients signed an informed consent form B CT acquisition and contouring CT scans were made using a LightSpeed RT 4s helical CT model (GE, Tokyo, Japan) with 25 5 mm slice spacing Patients were in the supine position and immobilized with a thermoplastic head shoulder mask accommodated on a VersaBoard immobilizer device (JRT Associates, Elmsford, NY) A planning CT scan (CT plan ) was acquired one week before RT treatment Second and third CT scans were performed during the course of treatment at the 15th ( ) and 25th ( ) fractions Patient weight was recorded before treatment and at weekly intervals during therapy The Eclipse version 75 (Varian Oncology Systems, Palo Alto, CA) treatment planning system was used for delineation and dose distribution calculations Target volumes and normal tissues were manually contoured by a physician on each axial slice of the CT plan using MRI or contrast-enhanced CT The definition of volumes was in accordance with ICRU Reports 50-62, (19,20) but dose-volume parameters were reported according to the new ICRU Report 83 (21) IMRT recommendations Gross tumor volume (GTV) included the primary tumor and affected lymph nodes The GTV was expanded to include the high-risk regions (CTV2) and

3 103 Beltran et al: Dose variations in H&N IMRT 103 the low risk nodal regions (CTV1) To compensate for geometrical uncertainties such as setup and organ motion, a 5 mm margin was automatically added to CTVs to obtain the planning target volume (PTV) In order to avoid dose compensation in the build-up region, in cases with no skin infiltration, the PTVs were manually modified excluding areas where the distance to the skin was less than 3 mm Although these modified PTVs were used during optimization process, the absorbed dose was reported over the whole PTV Prescribed doses were between Gy for PTV1 and Gy for PTV2 The critical structures contoured were: the parotid glands, spinal cord, mandible, eyes, oral cavity, brainstem, lips, cochleae, brain, and lower middle neck structures comprising the pharyngeal constrictors, glottic-supraglottic larynx, and the esophagus To avoid conflict between planning aims when OARs overlapped with PTVs, the former OARs were then automatically recontoured, excluding the region within PTV The modified OARs were used in the optimization process, but the final OAR dose goals were evaluated in the entire OAR A limited external volume structure was contoured, representing the volume inside the external body contoured from the upper level of the PTV1 to the upper neck treatment area, thus avoiding the presence of the shoulders This volume was added with the intention to correlate anatomical changes inside the treatment area with any weight change C Treatment planning IMRT treatment plan was generated on the CT plan with seven or nine 6 MV fields, using the simultaneous integrated boost (SIB) technique, treating the entire neck with IMRT but avoiding matching fields (22) The IMRT plans were optimized using an inverse planning algorithm, namely Helios 8005 (Varian Oncology Systems) The final dose distribution was calculated using the Pencil Beam Convolution 8005 with heterogeneity correction and 5 mm grid resolution Optimization goals were as follows: 1) prescription doses (D pres ) must encompass at least 95% of target volumes; 2) near-minimum absorbed doses (D 98% ) of PTVs should be higher than 93% of D pres ; 3) the near-maximum absorbed dose (D 2% ) of the PTVs should be less than 115% of D pres ; 4) PTV2 should be considered as the highest priority target volume High priority constraints to normal critical structures were: no more than 10 cm 3 of spinal cord could receive more than 48 Gy; 2) no more than 1% of brainstem could receive more 54 Gy; 3) D 2% for mandible should be less than 70 Gy; 4) the parotid gland volume receiving 26 Gy should be less than 50% in at least one gland; 5) D 2% of normal tissue should be less than D pres Low priority constraints that should not compromise target coverage were: 1) the mean absorbed dose (D mean ) covering lower middle neck, oral cavity, and lips should be less than 40 Gy; 2) eyes D 2% should be less than 50 Gy; 3) cochleae D 2% should be less than D pres All patients were treated with a Clinac 2100 accelerator (Varian Oncology Systems) with Millenium MLC - 80 leaves of 1 cm width in a Dynamic mode In order to reduce systematic setup errors, portal images were acquired periodically, and corrections were made using a weekly offline protocol D Manual adaptive contouring A simplified methodology was designed to evaluate volume variation during treatment with no attempt to modify the initial PTVs were registered using the initial reference marks and bony anatomy All contoured structures of CT plan were copied on the Following this, all contours were manually adapted for any anatomical changes For PTVs, efforts were made to maintain the original clinical volumes, and were modified only to be consistent with the new anatomy for instance, in cases where PTV extended beyond the skin or overlap areas limited by bones such as mandible and vertebra We are well aware that PTV changes during the course of RT could arise both from anatomical variations and from clinical response (ie, shrinkage and/or chemotherapy) Although the exact PTV in

4 104 Beltran et al: Dose variations in H&N IMRT 104 each stage of the treatment remains a controversial subject, we had chosen this particular contouring methodology because the idea of the study was to assess only dose variations arising from anatomic changes and not from a clinical response This methodology was used previously by other authors (16) In order to eliminate differences in volumes due to interobserver variability, the three scans of each patient were contoured by the same physician The initial plan was calculated at the and dose-volume differences related to CT plan were assessed on PTVs and organs at risk E Statistical analysis Comparisons of dose-volume parameters were assessed among all three CTs Correlation between volume changes and weight loss was evaluated All dose-volume parameters were reported following the ICRU 83 recommendations The analyzed variables for GTV and PTV were: 1) volume, and 2) D 2%, D 98%, and D 50% For OARs, the studied variables were: 1) volume, and 2) D 2%, D mean, and 3) volume receiving absorbed dose D (V D ), where D is the absorbed dose which, if exceeded within some volume, has a high probability of causing a serious complication D is specifically defined for each structure A random effects model for repeated measurements was fitted to assess differences between the planning CT and later CTs A value of p <005 was considered significant All analyses were performed with STATA 101 (StataCorp 2009 Statistical Software: Release 101 College Station, TX) III Results A Patient characteristics Between November 2008 and March 2010, a total of 16 patients with bilateral neck and supraclavicular nodes treated with IMRT were included Table 1 shows patient characteristics Fourteen patients received radical treatment consisting of IMRT 70 Gy in 33 fractions of 212 Gy/fr, and systemic therapy specifically, Cisplatin for 13 of them (100 mg/m 2 ; days 1, 22, 43) and a weekly administration of Cetuximab (anti-egfr) for the remaining patient Two patients received postoperative IMRT with Gy in fractions of Gy/fr, respectively Table 1 Patients characteristics N % Age Mean (range) (29-77) years Gender Male Female Primary site Nasopharynx 1 63 Oropharynx Oral Cavity Hypopharynx 1 63 Unknown T Stage Tx T1-T T T N Stage N N N N3 1 63

5 105 Beltran et al: Dose variations in H&N IMRT 105 B Volume and weight changes The average relative weight loss with regard to the initial weight was statistically significant, with a reduction of 3% (p = 00009) and 45% (p = < 00001) for, respectively One of the patients showed a weight gain of 55% at and 7% at A new mask was required at due to this increase Significant changes were found at the limited external volume, with an average decrease of 3% on both CTs (a range of: -163 to 129 for and -164 to 111 for ), with the maximum values corresponding to the sole patient with weight gain Correlation between the weight change and the limited external volume variations was significant, with p = 0006 for and p = 0001 for with respect to the CT plan One patient showed an important decrease in their limited external volume without weight loss (ie, due exclusively to tumor shrinkage) Of the remaining patients, 10 (63%) exhibited weight loss which was more significant at than at, and 4 (25%) suffered weight loss during the three first weeks, after which their weights remained stable Differences between the initial average volumes measured at CT plan and the two subsequent CTs were assessed for target volumes and OARs For target structures, only PTV2 had a significant volume decrease of 13% (range: -582, 207) at the The parotid glands showed a progressive mean volume reduction of 22% at and 30% at, corresponding to a mean reduction of 14% per treatment day (td) No other OAR showed a significant volume variation Mean volumes, averaged over the 16 patients, and p values are shown on Table 2 for the PTVs and the OARs with statistically significant changes only Ta b l e 2 Volumes with significant changes on in relation to CT plan Limited External Contralateral Ipsilateral PTV2 Contour Parotid Gland Parotid Gland Mean a (SD) p Mean (SD) p Mean (SD) p Mean (SD) p CT plan 1308 (731) 1692 (412) 1871 (103) 192 (106) 1167 (548) (402) (66) < (83) (535) (415) (64) < (72) <0001 a The mean value is the average volume between 16 patients, in cm 3 SD is the standard deviation; p < 005 is statistically significant

6 106 Beltran et al: Dose variations in H&N IMRT 106 C Dosimetric changes on target volumes Table 3 shows target volume averaged dose parameters at CT plan,, Values are presented as a percentage of D pres of each PTV Average D 2% values increased in all target volumes, with the most significant increase seen at In contrast, the dose covering the 95% and 98% of the volume decreased significantly at for PTV2 and in both CTs for PTV1 Ta b l e 3 Averaged dose-volume parameters on CT plan,, for target volumes Target D 2% D 50% D 95% D 98% Volume Mean a (SD) p Mean (SD) p Mean (SD) p Mean (SD) p GTV CT plan 1114 (3) 1071 (25) 1037 (2) 1030 (17) 1126 (37) (27) (28) (43) (47) (27) (25) (25) 0616 PTV2 CT plan 1103 (31) 1051 (17) 100 (0) 976 (13) 1121 (46) (27) (7) (93) (47) (23) (36) (5) 0348 PTV1 CT plan 1270 (64) 111 (45) 1012 (3) 982 (28) 1300 (69) < (57) (67) (11) (68) < (55) (7) (11) 0008 a All values are averaged percentages of D pres for each PTV and standard deviation (SD) D V absorbed dose that covers the fractional volume V A value of p < 005 is statistically significant The prescribed volume was 95% of PTV2 so D 50% values are higher than D 95% For PTV1, D 50% and D 2% are high because of the influence of high dose areas close to PTV2

7 107 Beltran et al: Dose variations in H&N IMRT 107 D Dosimetric changes on organs at risk Table 4 summarizes dose distribution changes on OAR, which showed some significant variation between planning CT and All reported doses were percentages of D pres For the ipsilateral parotid gland, there was a D m and V 26Gy significant increase at the of 47% and 63%, respectively For the contralateral parotid gland, there were significant increases in the following: D m (36% and 61%); D 2% (59% and 77%), and in the V 26Gy (74% and 104 %) For the spinal cord, the most notable dose increase was observed at, measuring a D 2% increase of 25% or 18 Gy Mean absorbed doses increased at in the following structures: the lips (38%, 53%), the oral cavity (35%, 25%), and lower middle neck structures (19% and 16%) For lips, V 20Gy increased in both CTs by 67% and 71%, respectively V 40Gy increased in and in the following organs: the oral cavity (57% and 33%), and lower middle neck structures (54% and 37%) No significant dose changes were found in the remaining OARs, namely the eyes, cochlea, brainstem, and brain No significant correlation was found between target and OAR dose increases with neither patient weight loss nor volume changes Ta b l e 4 Organs at risk with statistically significant dose changes between planning CT,, Normal D 2% D mean V b D Structure Mean a (SD) p Mean (SD) p Mean (SD) p Ipsi Parotid CT plan 897 (97) 445 (63) 497 (157) Gland 905 (125) (109) ( 203) 0285 D = 26Gy 938 (106) (111) (197) 0024 Contra Parotid CT plan 807 (113) 428 (52) 482 (104) Gland 855 (92) (63) (11) 0041 D = 26 Gy 869 (128) (82) (144) 0004 Mandible CT plan 1002 (58) 643 (57) 98 (89) D = 66 Gy 101 (58) (6) (93) (57) (66) (93) 0091 Oral Cavity CT plan 908 (101) 638 (141) 565 (251) D =40 Gy 945 (97) < (142) (224) (103) (147) (254) 0098 Middle low CT plan 878 (106) 633 (82) 603 (243) neck 913 (12) (81) (227) 0001 D = 40 Gy 897 (132) (87) (225) 0024 Lips CT plan 631 (168) 424 (114) 815 (165) D = 20 Gy 679 (17) (134) (158) (195) (145) < (135) 0006 Spinal cord CT plan 629 (35) 00 (0) D = 48 Gy 654 (72) (1) (52) (04) 0013 a The mean value is the average data between 16 patients and SD is the standard deviation D V represents the absorbed dose that covers the fractional volume V, and is expressed as a % of the prescribed dose b V D means percentage of total volume receiving a D dose For spinal cord volume it is in cc A value of p < 005 is statistically significant

8 108 Beltran et al: Dose variations in H&N IMRT 108 IV DISCUSSION A limitation of our work is the difficulty to separate influences over dose distribution due to rigid errors (ie, interfractional setup and intrafractional variations), and nonrigid anatomical changes during the course of the treatment Additionally, our results have to be interpreted with a degree of caution as some of the dose variations with respect to the initial plan are small and can therefore be affected by other variables, such as calculation grid size and random coregistration variability in the CTs (23) Finally, although statistical models attempt to reduce the impact of extreme variations, such as the patient who gained weight in this study, the sample size can significantly affect results, as any variation will have more influence in a smaller sample Despite the limited number of patients entered in our study (16), an important part of our results were nevertheless statistically significant Furthermore, our sample size is also larger than most used in published works related to this topic for example, studies carried out by Barker et al, (8) Hansen et al, (16) Robar et al, (13) Lee et al, (11,15) and Castadot et al (9) included 14, 13, 15, 10, and 10 patients, respectively Taking into account all of the above factors, the average data shown in Tables 3 and 4 could therefore help to identify dosimetric variables at risk of suffering changes during patient radiation treatment The study shows that HNC patients treated with IMRT undergo weight changes correlated with limited external volume variations, suggesting that patient weight may be a reliable parameter to detect changes in irradiated body areas Weight loss is appreciable after the third week of RT treatment Despite attempts being made to maintain the original PTVs size, volume change was significant in PTV2 because, in many cases, volumes lying beyond the external contour had been modified The target coverage loss during the first part of the treatment, in which no significant target volume changes occurred, can be related to the anatomical changes observed (ie, changes in the external volume) Our results coincide with Ahn et al, (18) who studied 23 HNC patients undergoing regular scans and found a loss of PTV coverage at approximately the 11th fraction, which was recovered in the posterior scans The parotid glands suffered a significant volume reduction and dose increase as treatment advanced We show a significant averaged increase in D mean in the parotid glands of 54% (38 Gy) at the 25th fraction, consistent with Lee et al, (15) who reported a difference between planned and received mean doses of less than 10% in 70% of studied patients In our study, the parotid glands suffered a mean reduction of 14%/td, consistent with 15%/td in the study by Bhide et al, (12) although a little higher than Castadot et al and Lee et al (9,15) of 09% 10%/td No correlation was found between volume reduction and dose This may be due to one of many factors including a potential medial translation of the glands into high-dose areas, as reported by several authors (8,9,11) None of the remaining normal tissues studied suffered volume variations Nonetheless, the spinal cord and mandible showed a D 2% increase The oral cavity, lips, and lower middle neck structures suffered a mean dose increase significant in the two CTs, indicating that body volume reduction inside the treatment area most likely contributed to a dose increase Dose variation over these structures should therefore be considered For HNC patients treated with 3D CRT, except in the case of larynx and hypopharynx tumors, a central block is usually employed in the anterior neck field in order to avoid dysphasia and swallowing problems related with middle neck structure irradiation In this study, lower middle neck structures were included because treating the entire neck with IMRT nonmatching fields decreases the risk of hot or cold spots due to errors in collimator positioning, while at the same time increases the dose in the lower middle neck (24) In our statistical data, the volume of middle neck structures receiving more than 40 Gy was significantly increased in both CTs with an average increment of 46%

9 109 Beltran et al: Dose variations in H&N IMRT 109 Dose deviations in relation to the initial dose in organs such as the oral cavity, lips, and middle lower neck have not yet been studied, and we think therefore that it is of interest to evaluate the effect of the above deviations on patients entered in our study Table 5 shows the dose variation range of D mean and V D with respect to initial dose in the aforementioned structures in 16 of the patients The number of patients with dose increments up to 10% is reported; the number in parenthesis indicates patients coinciding in the two CTs The number of patients exceeding a 10% difference is larger in V D than in D mean In the majority of cases, patients with values above 10% in V D are not necessarily the same patients in whom D mean was increased These specific OARs should be contoured and monitored in order to know if the initial plan remains suitable during the course of the treatment To correct the effect of anatomical changes over dose distribution during the treatment, an adaptive radiotherapy (ART) approach is used Schwartz and Dong (25) have reviewed current investigations of ART in HNC, and conclude that ART remains an unsolved problem because the optimal frequency, utilization, and clinical impact of ART remain undefined Moreover, advances in automated planning techniques based on deformable image registration will help to improve the feasibility of ART in HNC patients ART and deformable image registration are still in development and are, therefore, not clinically implemented in the majority of hospitals Although replanning during the course of treatment is a time-consuming process, it has potential advantages and is readily accessible for many centers It should be stressed that it will be necessary to identify which patients in particular would benefit from replanning For instance Ahn et al (18) indicated that only 15 out of 23 patients (65%) benefitted from a new plan Recently, Zhao et al (26) showed that nasopharyngeal carcinoma patients who have clinically identified anatomic changes during the course of IMRT might potentially benefit from replanning For now, if ART rationale were used, the benefit of replanning would have to be analyzed individually There are many issues which could determine the need for a replan: clinical patient conditions, and percentages of initial dose distribution variations for each PTV and OARs The decision to consider suitable dose distribution is always a compromise between dose in target volumes and dose in OARs Furthermore, both facilities and human/economical resources could determine the final decision for replanning These complex factors are beyond the scope of this work but until now, no predictive factors that might identify the need for replanning have been reported It is therefore essential to establish a rational adaptive RT scheme compliant with defined dosimetric criteria The dosimetric criteria employed to select which patients could benefit most from replanning should be based on the knowledge of spatial dose variations on both target volumes and organs at risk during the course of treatment Dose variations reported in our study may therefore be of some help for future investigations concerning adaptive radiotherapy Ta b l e 5 Dose variation range of D mean and V D, for the oral cavity, lips, and middle lower neck, and number of patients with dose increase up to 10% D mean (%) V D (%) a Patients with dose Patients with dose Normal Structure Range increase up 10% Range increase up 10 Oral Cavity -25, , D =40 Gy -24, , 21 2 (1) Middle low neck -1, , D = 40 Gy -23, , (0) Lips -34, , 29 5 D = 20 Gy -05, (1) -25, 29 3 (3) a V D means percentage of total volume receiving a D dose

10 110 Beltran et al: Dose variations in H&N IMRT 110 V Conclusions Variations in patient positioning and anatomical changes during IMRT for head-and-neck cancer can modify dosimetric parameters and may therefore have clinical implications on local control and toxicity We have seen that the dose distribution over target volumes shows a decrease of coverage in the first part of the treatment and an overdosage towards the final part of the treatment The mean dose in the parotid glands showed significant increases both for the contralateral than ipsilateral parotid gland The present work has included structures related with new IMRT toxicities with the oral cavity, lips, brain, and lower middle neck irradiation It is, to our knowledge, the first study analyzing the influence of volume changes over dose distribution on these particular organs at risk Results have shown that there is a significant dose increase in the oral cavity, lips, and lower middle neck, although these structures did not present volume variations Behavior of dose distribution over target volumes and OARs depends on several aspects, namley particular volume changes, localization, and the irradiation technique employed The IMRT technique implies the irradiation of a larger number of OARs than conventional 3D CRT, some of them at high doses In conclusion, appropriate OARs have to be contoured and monitored in order to know if the initial plan remains suitable during the course of the treatment Reported dosimetric data can help to identify patients who could benefit from adaptive radiotherapy References 1 Huang D, Xia P, Akazawa P, et al Comparison of treatment plans using intensity-modulated radiotherapy and three-dimensional conformal radiotherapy for para-nasal sinus carcinoma Int J Radiat Oncol Biol Phys 2003;56(1): Chao KS, Ozyigit G, Blanco AI, et al Intensity-modulated radiation therapy for oropharyngeal carcinoma: Impact of the tumor volume Int J Radiat Oncol Biol Phys 2004;59(1): Miles EA, Clark CH, Urbano MT, et al The impact of introducing intensity modulated radiotherapy into routine clinical practice Radiother Oncol 2005;77(3): Scott-Brown M, Miah A, Harrington K, Nutting C Evidence-based review: Quality of life following head and neck intensity-modulated radiotherapy Radiother Oncol 2010;97(2): Nutting CM, Morden JP, Harrington KJ et al Parotid-sparing intensity modulated versus conventional radiotherapy in head and neck cancer (PARSPORT): a phase 3 multicentre randomised controlled trial Lancet Oncol 2011;12(2): Mechalakos JG, Hunt MA, Lee NY, Hong LX, Ling CC, Amols H Using an onboard kilovoltage imager to measure setup deviation in intensity-modulated radiation therapy for head-and-neck patients J Appl Clin Med Phys 2007;8(4): Van Herk M, Remeijer P, Rasch C,Lebesque JV The probability of correct target dosage: dose-population histograms for deriving treatment margins in radiotherapy Int J Radiot Oncol Biol Phys 2000;47(4): Barker JL, Garden AS, Ang KK, et al Quantification of volumetric and geometric changes occurring during fractionated radiotherapy for head-and-neck cancer using an integrated CT/linear accelerator system Int J Radiat Oncol Biol Phys 2004;59(4): Castadot P, Geets X, Lee JA, Christian N and Grégoire V Assessment by a deformable registration method of the volumetric and positional changes of target volumes and organs at risk in pharyngo-laryngeal tumors treated with concomitant chemo-radiation Radiother Oncol 2010;95(2): Vasquez Osorio EM, Hoogeman MS, Al-Mamgani A, Teguh DN, Levendag PC and Heijmen BJM Local anatomic changes in parotid and submandibular glands during radiotherapy for oropharynx cancer and correlation with dose, studied in detail with nonrigid registration Int J Radiat Oncol Biol Phys 2008;70(3): Lee C, Langen KM, Lu W, et al Evaluation of geometric changes of parotid glands during head and neck cancer radiotherapy using daily MVCT and automatic deformable registration Radiother Oncol 2008;89(1): Bhide SA, Davies M, Burke K, et al Weekly volume and dosimetric changes during chemoradiotherapy with intensity-modulated radiation therapy for head and neck Cancer: a prospective observational study Int J Radiat Oncol Biol Phys 2010;76(5): Robar JL, Day A, Clancey J, et al Spatial and dosimetric variability of organs at risk in head-and-neck intensitymodulated radiotherapy Int J Radiat Oncol Biol Phys 2007;68(4): Han C, Chen YJ, Liu A, Schultheiss T, Wong JY Actual dose variation of parotid glands and spinal cord for nasopharyngeal cancer patients during radiotherapy Int J Radiat Oncol Biol Phys 2008;70(4): Lee C, Langen KM, Lu W, et al Assessment of parotid gland dose changes during head and neck cancer radiotherapy using daily megavoltage computed tomography and deformable image registration Int J Radiat Oncol Biol Phys 2008;71(5):

11 111 Beltran et al: Dose variations in H&N IMRT Hansen EK, Bucci MK, Quivey JM, Weinberg V, Xia P Repeat CT imaging and replanning during the course of IMRT for head-and-neck cancer Int J Radiat Oncol Biol Phys 2006;64(2): Wang W, Yang H, Hu W et al Clinical study of the necessity of replanning before the 25th fraction during the course of intensity-modulated radiotherapy for patients with nasopharyngeal carcinoma Int J Radiat Oncol Biol Phys 2010;77(2): Ahn PH, Chen CC, Ahn AI, et al Adaptive planning in intensity-modulated radiation therapy for head and neck cancers: single-institution experience and clinical implications Int J Radiat Oncol Biol Phys 2010;80(3): International Commission on Radiation Units and Measurements (ICRU) Report 50: Prescribing, recording, and reporting photon beam therapy Bethesda: ICRU, International Commission on Radiation Units and Measurements (ICRU) ICRU Report 62: Prescribing, recording, and reporting photon beam therapy (Supplement to ICRU Report 50) Bethesda, MD: ICRU; International Commission on Radiation Units and Measurements ICRU Report 83: Prescribing, recording, and reporting photon beam intensity modulated radiation therapy (IMRT) J ICRU 2010;10(1) 22 Wu Q, Mohan R, Morris M, Lauve A, Schmidt-Ullrich R Simultaneous integrated boost intensity-modulated radiotherapy for locally advanced head-and-neck squamous cell carcinomas I: Dosimetric results Int J Radiat Oncol Biol Phys 2003;56(2): van Beek S, van Kranen S, Mencarelli A, et al First clinical experience with a multiple region of interest registration and correction method in radiotherapy of head-and-neck cancer patients Radiother Oncol 2010;94(2): Chuang C, Xia P, Akazawa P, Verhey L, Quivey, Lee N Comparison of three treatment techniques involving IMRT fields for head and neck cancers [abstract] Int J Radiat Oncol Biol Phys 2002;54(S2): Schwartz DL and Dong L Adaptive radiation therapy for head and neck cancer Can an old goal evolve into a new standard? J Oncol 2011 Epub 2010 Aug Zhao L, Wan Q, Zhou Y, Deng X Xie C, WuS The role of replanning in fractionated intensity modulated radiotherapy for nasopharyngeal carcinoma Radiother Oncol 2011;98(1):23 27